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Cardiac spheroids as a human model for inflammation induced cardiac dysfunction.

Simon Athlin1,2, Niklas Steger2, Jishamol Thazhath Veettil3

  • 1School of Medical Science, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

Biofabrication
|February 26, 2026
PubMed
Summary

Human cardiac spheroids, complex 3D microtissues, effectively model inflammation-induced heart dysfunction. This study shows these models accurately reflect inflammatory responses and functional decline, aiding therapeutic development.

Keywords:
3D cardiac modelscardiac dysfunctioncardiac spheroidscontractilityinflammationlipopolysaccharide (LPS)mitochondrial respiration

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Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Biomedical Engineering

Background:

  • Inflammatory signaling critically impacts cardiac dysfunction in sepsis, myocarditis, and heart failure.
  • Current in vitro models lack the multicellular complexity for accurate human cardiac pathology recapitulation.

Purpose of the Study:

  • To utilize human cardiac spheroids as a physiologically relevant model for studying lipopolysaccharide (LPS)-induced cardiac inflammation.
  • To assess the impact of inflammation on mitochondrial metabolism and contractile function in a multicellular cardiac model.

Main Methods:

  • Human cardiac spheroids composed of cardiomyocytes, fibroblasts, and endothelial cells were developed.
  • Lipopolysaccharide (LPS) was used to induce inflammation, followed by assessment of cytotoxicity (LDH release).
  • Transcriptional and protein levels of inflammatory markers (TLR2, IL6, TNF, CXCL8, CCL2), mitochondrial function, and contractility were analyzed.

Main Results:

  • LPS stimulation induced a robust inflammatory response without significant cytotoxicity.
  • Significant upregulation and secretion of key inflammatory mediators were observed.
  • Mitochondrial respiration, ATP production, and maximal capacity were significantly reduced.
  • Cardiac spheroid contractility was impaired, showing reduced beat rate and altered contraction/relaxation dynamics.

Conclusions:

  • Human cardiac spheroids provide a physiologically relevant platform for studying multicellular inflammatory responses in the heart.
  • This model demonstrates that inflammation compromises mitochondrial metabolism and mechanical performance.
  • The spheroid model is valuable for investigating innate immune activation and screening anti-inflammatory therapies for cardiac dysfunction.